Preliminary work suggests that measures based on gait dynamics may be useful in assisting in the functional assessment of chronic disease and the resulting disability. Approximately forty nine million Americans have a chronic disability. These disabilities often affect physical function and mobility, limit activities, reduce independence, and decrease quality of life. However, the absence of precise, quantitative and objective measures of function that can be administered in multiple settings (e.g., in the clinic) limits our ability to objectively monitor disease progression and assess the efficacy of new therapeutic interventions. The overall goal of the present application is to extend our preliminary findings to evaluate how measures of gait dynamics may be used in functional assessment of chronic disease. Because gait dynamics may serve as a sensitive and clinically relevant index of functional ability in the evaluation of intervention trials and may be useful in augmenting early diagnosis of chronic disease, we believe it is critical to understand its origins. A secondary goal of this project, therefore, is to quantitatively characterize the factors that contribute to altered gait dynamics. The third objective of this application is to develop practical measures of gait dynamics that can be used to augment clinical assessment of chronic disabling disease. In this project, we will study the relationship between chronic disease (i.e., knee osteoarthritis, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis), gait dynamics, and functional status and evaluate how gait dynamics change with disease progression and in response to therapeutic interventions, including exercise and deep brain stimulation. The results of the study will provide new insight into the physiology and adaptations of chronic disease, the efficacy of different therapeutic interventions, and may also provide a new method to augment functional assessment of chronic disability.